Eclipse was foaled during and named after the solar eclipse of 1st April 1764, at the Cranbourne Lodge Stud of his breeder, Prince William Augustus, Duke of Cumberland. It was at this stud that his sire, the Jockey Club Plate winner, Marske (by Squirt from The Ruby Mare) stood, his dam, Spiletta (foaled 1749) was by Regulus, by the Godolphin Arabian. Eclipse was a brother to the successful broodmare, Proserpine. They were inbred to Snake in the fourth generation of their pedigree. After the death of Prince William in 1765, Eclipse was sold for 75 guineas to a sheep dealer from Smithfield, William Wildman.

Eclipse started racing at the age of five on 3rd May 1769 at Epsom. After his second victory in a race in May 1769 the Irish adventurer Colonel Dennis O'Kelly purchased Eclipse in two parts (50 percent in June 1769 for 650 guineas, 50 percent in April 1770 for 1,100 guineas). Supposedly, at this time Captain Denis O'Kelly used the famous phrase "Eclipse first and the rest nowhere," before making his bets for this race. At that time, a horse that was more than 240 yards behind the lead was said to be nowhere. His jockey was John Oakley, supposedly the only jockey who could handle Eclipse's temperamental manner and running style of holding his nose very close to the ground. Eclipse won the race easily.

Eclipse won 18 races, including 11 King's Plates, supposedly without ever being fully extended and proving far superior to all competition. During this time he raced over 63 miles and walked 1,400 miles to race meetings across England.

In 1771, Eclipse was retired to stud after a racing career of about 17 months due to lack of competition as nobody was betting on rival horses. Initially he stood at O'Kelly's Clay Hill Stud, near Epsom (Surrey), for a fee of 10 guineas which rose rapidly to 25 and then to 50 guineas a mare. During 1788, he was relocated to Cannons Stud, Edgware (Middlesex).

Overall, Eclipse sired 344 winners of more than ₤158,000 (although the number varies with different reports, ranging from 325 to 400).

Eclipse died due to an attack of colic on 27th February 1789, at the age of 24. His skeleton is now housed at the Royal Veterinary College, Hertfordshire, in the Learning Resource Centre named after him, although it cannot be said for certain whether all the bones displayed are really from Eclipse. His hooves were made into inkstands, although the fact that there are at least five Eclipse-hoof inkstands casts some doubt on the authenticity of some. Hairs from his tail have also been used for decorations.

A necropsy on Eclipse found that he had an abnormally large heart (weighing 14 lbs). This trait, referred to in the context of thoroughbreds as the "X-Factor" has been seen occasionally in his descendants, including Secretariat and Phar Lap.